Tags

Type your tag names separated by a space and hit enter

Growth inhibition of human breast cancer cells in vitro with an antibody against the type I somatomedin receptor.
Cancer Res. 1989 Nov 15; 49(22):6237-41.CR

Abstract

Insulin and insulin-like growth factors (IGFs) stimulate the growth of human breast cancer cells in vitro. The type I somatomedin receptor (SR), expressed in these cells, may mediate the mitogenic effects of these peptides. We have examined the effect of type I SR blockade on human breast cancer growth with a monoclonal antibody (alpha-IR3) that blocks the receptor binding domain. alpha-IR3 inhibited binding of 125I-IGF-I in all breast cancer cell lines tested. Binding affinity of alpha-IR3 was 2 to 5 times higher than that of IGF-I in MDA-231 (Kd 2.1 nM) and MCF-7 cells (Kd 0.6 nM), respectively. In the presence of 10% calf serum, the antibody inhibited anchorage-independent growth of six of seven breast cancer cell lines. This inhibition was reversible with excess IGF-I. In serum-free medium, alpha-IR3 blocked IGF-I-stimulated DNA synthesis in four of four breast cancer cell lines (MCF-7, ZR75-1, MDA-231, and HS578T). However, the antibody did not inhibit basal growth of any of the breast cancer cell lines in serum-free conditions. In three estrogen receptor-positive, estrogen-responsive breast cancer cell lines (MCF-7, ZR75-1, and T47D), type I SR blockade with alpha-IR3 failed to block estrogen-stimulated DNA synthesis or cell proliferation, indicating that secreted IGF activity is not the sole mediator of the growth effects of estrogen. In conclusion, antibody-mediated type I SR blockade does not inhibit basal growth of breast cancer cells under serum-free conditions, arguing against a critical autocrine role of endogenously secreted IGF activity in vitro. However, type I SR blockade inhibits breast cancer cell growth in the presence of serum, suggesting that serum IGFs might be critical endocrine or paracrine regulators of human breast cancer.

Authors+Show Affiliations

Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2553250

Citation

Arteaga, C L., and C K. Osborne. "Growth Inhibition of Human Breast Cancer Cells in Vitro With an Antibody Against the Type I Somatomedin Receptor." Cancer Research, vol. 49, no. 22, 1989, pp. 6237-41.
Arteaga CL, Osborne CK. Growth inhibition of human breast cancer cells in vitro with an antibody against the type I somatomedin receptor. Cancer Res. 1989;49(22):6237-41.
Arteaga, C. L., & Osborne, C. K. (1989). Growth inhibition of human breast cancer cells in vitro with an antibody against the type I somatomedin receptor. Cancer Research, 49(22), 6237-41.
Arteaga CL, Osborne CK. Growth Inhibition of Human Breast Cancer Cells in Vitro With an Antibody Against the Type I Somatomedin Receptor. Cancer Res. 1989 Nov 15;49(22):6237-41. PubMed PMID: 2553250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Growth inhibition of human breast cancer cells in vitro with an antibody against the type I somatomedin receptor. AU - Arteaga,C L, AU - Osborne,C K, PY - 1989/11/15/pubmed PY - 1989/11/15/medline PY - 1989/11/15/entrez SP - 6237 EP - 41 JF - Cancer research JO - Cancer Res. VL - 49 IS - 22 N2 - Insulin and insulin-like growth factors (IGFs) stimulate the growth of human breast cancer cells in vitro. The type I somatomedin receptor (SR), expressed in these cells, may mediate the mitogenic effects of these peptides. We have examined the effect of type I SR blockade on human breast cancer growth with a monoclonal antibody (alpha-IR3) that blocks the receptor binding domain. alpha-IR3 inhibited binding of 125I-IGF-I in all breast cancer cell lines tested. Binding affinity of alpha-IR3 was 2 to 5 times higher than that of IGF-I in MDA-231 (Kd 2.1 nM) and MCF-7 cells (Kd 0.6 nM), respectively. In the presence of 10% calf serum, the antibody inhibited anchorage-independent growth of six of seven breast cancer cell lines. This inhibition was reversible with excess IGF-I. In serum-free medium, alpha-IR3 blocked IGF-I-stimulated DNA synthesis in four of four breast cancer cell lines (MCF-7, ZR75-1, MDA-231, and HS578T). However, the antibody did not inhibit basal growth of any of the breast cancer cell lines in serum-free conditions. In three estrogen receptor-positive, estrogen-responsive breast cancer cell lines (MCF-7, ZR75-1, and T47D), type I SR blockade with alpha-IR3 failed to block estrogen-stimulated DNA synthesis or cell proliferation, indicating that secreted IGF activity is not the sole mediator of the growth effects of estrogen. In conclusion, antibody-mediated type I SR blockade does not inhibit basal growth of breast cancer cells under serum-free conditions, arguing against a critical autocrine role of endogenously secreted IGF activity in vitro. However, type I SR blockade inhibits breast cancer cell growth in the presence of serum, suggesting that serum IGFs might be critical endocrine or paracrine regulators of human breast cancer. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/2553250/Growth_inhibition_of_human_breast_cancer_cells_in_vitro_with_an_antibody_against_the_type_I_somatomedin_receptor_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=2553250 DB - PRIME DP - Unbound Medicine ER -